Modern treatment methods have led to major improvements in the survival rate of children with Wilms' tumor. Combined therapy using surgery, radiation therapy and chemotherapy now cures 90% of patients. Those with tumors of unfavorable histology and those with metastases, either synchronous or metachronous, are at higher risk. Their survival is in the 50-65% range, and better treatments clearly are needed. At the same time, all therapies have their associated risks and complications, and some are costly and inconvenient. Refinements of therapy for children with a good outlook are therefore needed to increase efficiency, and reduce risks and costs. NWTS-4 is designed to achieve these objectives through better understanding of the renal tumors of childhood, their epidemiology and the late effects of successful therapy, while conducting clinical trials of novel therapies. These latter ask the following questions: (1) Can single daily doses of effective chemotherapeutic agents given more frequently over a shorter interval improve the outlook while decreasing costs and inconvenience? (2) Can such regimens incorporating new drugs improve the retrieval rate for patients with recurrent disease, and in so doing identify new agents for primary care? The NWTS thus is undertaking new tasks: the identification of new, effective chemotherapies; and the reduction of the socio-economic burdens of therapy while striving for more cures.